ABSTRACT/PROJECT SUMMARY Alzheimer?s disease and related dementias (ADRD) are responsible for a staggering personal, economic, and societal cost. This Administrative Supplement project will examine the degree to which hoarding disorder symptoms with a late age of onset (LOHD) are associated with blood-based measures of neurodegeneration and abnormal protein aggregation common in dementia, specifically plasma measures of neurofilament light chain (Nfl), amyloid, and tau. By determining the association of LOHD, which may be an early symptom of neurodegenerative disease and incipient dementia, with blood markers used to detect pathological processes in ADRD, this project will significantly advance our understanding of ADRD in older adults. This work holds significant promise to inform the development of more effective interventions to prevent or treat behavioral disturbance associated with ADRD, to identify behavioral markers of individuals a higher risk for ADRD, to clarify mechanisms contributing to accelerated cognitive decline in older adults, and to improve screening and recruitment efforts for studies investigating the earliest stages of ADRD. Hoarding disorder, a neuropsychiatric illness that was only recognized as a formal psychiatric diagnosis within the last 10 years, is common, occurring in up to 6% of adults over 55, and epidemiologically has more similarities to the dementias than it does to other psychiatric disorders. Hoarding symptoms are also much more common among individuals with dementia than in the general population, occurring in up to one third of individuals with ADRD. However, the relationship between LOHD and potential biomarkers of incipient dementia have never been examined. This proposal will address this critical scientific gap. Three hundred participants, 100 with LOHD, 100 with early onset hoarding (EOHD), and 100 age matched healthy controls (HC), will be recruited from the parent study: ?Hoarding disorder in older adults: cognition, etiology, and functional impact? (R01MH117114). Blood-based biomarkers of neurodegeneration (Nfl) and protein aggregation characteristic of Alzheimer?s disease (AD) and related dementias (tau and amyloid protein) will be measured for each participant. The relationship between plasma levels of these potential biomarkers and hoarding symptoms will be examined. Two core specific aims will be accomplished. These are: 1) To examine the association of blood-based measures of neurodegeneration and dementia with LOHD compared with EOHD and age matched healthy controls (HC), and 2) To determine whether there are relationships between these plasma biomarkers and measures of subjective cognitive decline and functional disability. A third exploratory aim will also examine whether a relationship exists between Nfl, a measure of general neurodegeneration, and medical comorbidities across all participants, but with a specific focus on those with hoarding symptoms. This project represents a unique, impactful, and cost-effective opportunity to advance our understanding of hoarding symptoms in ADRD.